Hydrophobic diacrylamide compound

ABSTRACT

A silyl protected diacrylamide compound is described. A method of forming such a compound includes mixing a silylation reagent with a hydroxylated diamine compound under first reactive conditions to form a product in a first solution, separating the product from the first solution, and mixing the product with acryloyl chloride under second reactive conditions in a second solution to form a silyl protected diacrylamide compound.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application claims benefit of U.S. Provisional Application No.61/597,060, filed Feb. 9, 2012, which is incorporated herein byreference in its entirety.

FIELD OF THE DISCLOSURE

This disclosure, in general, relates to protected diacrylamide compoundsand methods for making same.

BACKGROUND

Multi-functional compounds have a variety of uses. For example,multi-functional compounds find use in synthesis reactions to formsymmetric compounds or to form cyclic compounds. In another example,multi-functional compounds find use in polymerization reactions, forexample, as crosslinkers. Such crosslinkers can influence the physicalproperties of a polymer, such as glass transition temperature, or caninfluence mechanical properties, such as flexibility or shearresistance.

SUMMARY

In a first aspect, a compound has formula I below or an analog thereof,wherein R1 and R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R3, R4, R5, R6, and R7 are independentlyselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl,oxycarbonyl, aryl, ether derivatives thereof, a silyl, or a combinationthereof.

In a second aspect, a compound has the formula II below or an analogthereof, wherein R1 or R2 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof, and R3, R4, or R5 are independentlyselected from hydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl,acyl, aryl, ether derivatives thereof, or a combination thereof.

In a third aspect, a compound has the formula III below or an analogthereof, R1, R2, or R3 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof.

In a fourth aspect, a compound has the formula XII below or an analogthereof, wherein R4, R5, or R6 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof, and R1, R2, R3, R7, R8, or R9 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a combinationthereof.

In a fifth aspect, a compound has the formula XIII below or an analogthereof, wherein R4 or R5 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof, and R1, R2, R3, R6, R7, or R8 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a combinationthereof.

In a sixth aspect, a compound has the formula VII below or an analogthereof, wherein R1 or R2 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof or represent a direct bond between anitrogen and a hydroxylated carbon, and R3, R4, R5, R6, R7, R8, R9, orR10 are independently selected from hydrogen, alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, oxycarbonyl, aryl, ether derivativesthereof, silyl, or a combination thereof.

In a seventh aspect, a method of forming a compound includes mixing anactivated acrylate and a hydroxylated diamine compound to form ahydroxylated diacrylamide compound, separating the hydroxylateddiacrylamide compound, and mixing a silylation reagent with thehydroxylated diacrylamide compound under reactive conditions to form asilyl protected diacrylamide compound.

In an eighth aspect, a method of forming a compound includes mixing asilylation reagent with a hydroxylated diacrylamide under reactiveconditions to form silyl protected diacrylamide in a solution andseparating the silyl protected diacrylamide from the solution.

In a ninth aspect, a method of forming a compound includes mixing asilylation reagent with a hydroxylated diamine compound under firstreactive conditions to form a product in a first solution, separatingthe product from the first solution, and mixing the product with anactivated acrylate under second reactive conditions in a second solutionto form a silyl protected diacrylamide compound.

In a tenth aspect, a method of forming a polymer includes mixing in ahydrophobic phase, a monomer and a compound having a formula below, themonomer and the compound polymerizing to form the polymer.

In an eleventh aspect, a composition includes a non-aqueous solutionincluding a diacrylamide crosslinker and a free radical polymerizablemonomer.

DETAILED DESCRIPTION

In an exemplary embodiment, a multifunctional compound includes at leasttwo acrylamide functional groups or derivatives thereof, such as atleast two acrylamide terminal functional groups or methacrylamideterminal functional groups. A derivative of an acrylamide includes anacrylamide analog, such as methacrylamide, ethacrylamide, or acombination thereof. In particular, the multifunctional compound can bea diacrylamide. In another example, the multifunctional compound can bea diacrylamide analog, such as a di-methacrylamide. An exemplarydiacrylamide or analog thereof includes one or more hydrophilicfunctional groups other than the acrylamide functional groups. Inparticular, the hydrophilic functional group can include hydroxyl,amine, or a combination thereof. In a particular embodiment, thehydrophilic functional group is hydroxyl. The hydrophilic functionalgroup is protected with a protection group, such as a silyl groups andderivatives thereof, in which hydrogens are replaced with a hydrocarbon,halogen (e.g., Cl), trifluoromethanesulfonate, or a further silyl group.Such multifunctional compounds find particular use as precursors insynthesis reactions or function as crosslinkers in polymerizationreactions.

In a further embodiment, a multi- or diacrylamide compound can be formedfrom a multi- or diamine compound that includes a hydroxyl group. Forexample, the hydroxyl group can be protected with a silyl group, such asthrough reaction of the hydroxyl group with a halogenated silyl group.Following protection with silyl groups, the amine groups of the multi-or diamine can be reacted with an activated acrylate, such as acryloylchloride or acryloyl anhydride, to form a multi- or di-acrylamide. In analternative method, an acrylamide having one or more hydroxyl groups canbe protected by reacting the hydroxyl groups with a halogenated silylgroup.

In a particular example, a diacrylamide compound has the generalformula:

wherein R1 or R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R3, R4, R5, R6, or R7 are independentlyselected from hydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl,acyl, aryl, ether derivatives thereof, or a combination thereof. Whilethe vinyl groups are illustrated as including hydrogen, one or morehydrogens on the vinyl group can be placed with a halogen, such aschlorine, fluorine, or combination thereof. Alternatively, the compoundcan be an analog of the above compound.

In an example, R1 or R2 of formula I independently can be a C1-C6 alkyl,such as a methyl or ethyl group. In another example, R1 or R2independently can be hydroxyalkyl.

In another example, R6 or R7 independently can be selected from selectedfrom alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, oxycarbonyl,aryl, ether derivatives thereof, silyl, or a combination thereof. Forexample, R6 or R7 can be hydrogen. In a further example, R6 or R7 can bea C1-C6 alkyl, such as a methyl, ethyl, propyl, or butyl, or etherderivatives thereof. In particular, the alkyl can be linear or branched.For example, propyl includes n-propyl or iso-propyl, and butyl includesn-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additional example,R6 or R7 independently can be aryl, such as a phenyl, tolyl, xylyl, orpoly-aryl, such as naphthyl, or ether derivatives thereof.

In a further example, R3, R4, or R5 independently can be selected fromalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, etherderivatives thereof, or a combination thereof. For example, R3, R4, orR5 can be hydrogen. In a further example, R3, R4, or R5 can be a C1-C6alkyl, such as a methyl, ethyl, propyl or butyl, or ether derivativesthereof. For example, R3, R4, or R5 can be an ethyl, propyl or butyl, orether derivatives thereof. In particular, the alkyl can be linear orbranched. In example, at least one of R3, R4, or R5 can be a branchedalkyl. For example, propyl includes n-propyl or iso-propyl, and butylincludes n-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additionalexample, R3, R4, or R5 independently can be an aryl, such as a phenyl,tolyl, xylyl, or poly-aryl, such as naphthyl, or ether derivativesthereof.

In a particular example of formula I, R6 and R7 are hydrogen, providinga diacrylamide of the formula:

wherein R1 or R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R3, R4, or R5 are independently selected fromalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, etherderivatives thereof, or a combination thereof. While the vinyl groupsare illustrated as including hydrogen, one or more hydrogens on thevinyl group can be placed with a halogen, such as chlorine, fluorine, orcombination thereof. Alternatively, the compound can be an analog of theabove compound.

In an example, R1 or R2 of formula II independently can be a C1-C6alkyl, such as a methyl or ethyl group. In another example, R1 or R2independently can be hydroxyalkyl.

In a further example, R3, R4, or R5 independently can be selected fromalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, etherderivatives thereof, or a combination thereof. In a further example, R3,R4, or R5 can be a C1-C6 alkyl, such as a methyl, ethyl, propyl orbutyl, or ether derivatives thereof. For example, R3, R4, or R5 can bean ethyl, propyl or butyl, or ether derivatives thereof. In particular,the alkyl can be linear or branched. In example, at least one of R3, R4,or R5 can be a branched alkyl. For example, propyl includes n-propyl oriso-propyl, and butyl includes n-butyl, iso-butyl, sec-butyl, ortert-butyl. In an additional example, R3, R4, or R5 independently can bean aryl, such as a phenyl, tolyl, xylyl, or poly-aryl, such as naphthyl,or ether derivatives thereof.

In an example, R1 and R2 of formula II are methyl, providing adiacrylamide of the following formula:

wherein R1, R2, or R3 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof. While the vinyl groups areillustrated as including hydrogen, one or more hydrogens on the vinylgroup can be placed with a halogen, such as chlorine, fluorine, orcombination thereof. Alternatively, the compound can be an analog of theabove compound, such as a methacrylamide analog. For example, R1, R2, orR3 can be a C1-C6 alkyl, such as a methyl, ethyl, propyl or butyl, orether derivatives thereof. For example, R1, R2, or R3 can be an ethyl,propyl or butyl, or ether derivatives thereof. In particular, the alkylcan be linear or branched. In example, at least one of R3, R4, or R5 canbe a branched alkyl. For example, propyl includes n-propyl oriso-propyl, and butyl includes n-butyl, iso-butyl, sec-butyl, ortert-butyl. In an additional example, R1, R2, or R3 independently can bean aryl, such as a phenyl, tolyl, xylyl, or poly-aryl, such as naphthyl,or ether derivatives thereof.

In a particular example of formula III, R1, R2, and R3 are ethyl,providing a diacrylamide of the following formula, which has a log(p)value of 1.84.

In another example of formula III, R1 and R3 are methyl and R2 istert-butyl, providing a diacrylamide of the following formula, which hasa log(p) value of 1.8.

In an additional example of formula III, R1 and R2 are methyl and R3 isphenyl, providing a diacrylamide of the following formula, which has alog(p) value of 1.77.

In a further example of a multi-functional acrylamide compound, adiacrylamide compound has the following formula:

wherein R1 or R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof or represent a direct bond between a nitrogen and ahydroxylated carbon, and R3, R4, R5, R6, R7, R8, R9, or R10 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, oxycarbonyl, aryl, ether derivatives thereof, silyl,or a combination thereof. While the vinyl groups are illustrated asincluding hydrogen, one or more hydrogens on the vinyl group can beplaced with a halogen, such as chlorine, fluorine, or combinationthereof. Alternatively, the compound can be an analog of the abovecompound. In a further example, the compound can be monosilylated whereone of the silyl groups of the above formula is replaced with ahydroxide or alkoxy group.

In an example, R1 or R2 of formula VII independently can be a C1-C6alkyl, such as a methyl or ethyl group. In another example, R1 or R2independently can be hydroxyalkyl. In a particular example, R1 and R2represent a direct bond between a nitrogen and a hydroxylated carbon.

In another example, R6 or R7 independently can be selected from selectedfrom hydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl,oxycarbonyl, aryl, ether derivatives thereof, silyl, or a combinationthereof. For example, R6 or R7 can be hydrogen. In a further example, R6or R7 can be a C1-C6 alkyl, such as a methyl, ethyl, propyl, or butyl,or ether derivatives thereof. In particular, the alkyl can be linear orbranched. For example, propyl includes n-propyl or iso-propyl, and butylincludes n-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additionalexample, R6 or R7 independently can be aryl, such as a phenyl, tolyl,xylyl, or poly-aryl, such as naphthyl, or ether derivatives thereof.

In a further example, R3, R4, R5, R8, R9, or R10 independently can beselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl,ether derivatives thereof, or a combination thereof. In a furtherexample, R3, R4, R5, R8, R9, or R10 can be a C1-C6 alkyl, such as amethyl, ethyl, propyl or butyl, or ether derivatives thereof. Forexample, R3, R4, or R5 can be an ethyl, propyl or butyl, or etherderivatives thereof or R8, R9, or R10 can be an ethyl, propyl or butyl,or ether derivatives thereof. In particular, the alkyl can be linear orbranched. In example, at least one of R3, R4, or R5 can be a branchedalkyl or at least one of R8, R9, or R10 can be a branched alkyl. Forexample, propyl includes n-propyl or iso-propyl, and butyl includesn-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additional example,R3, R4, R5, R8, R9, or R10 independently can be an aryl, such as aphenyl, tolyl, xylyl, or poly-aryl, such as naphthyl, or etherderivatives thereof.

In an example of formula VII, R1 and R2 represent a direct bond betweennitrogen and a hydroxylated carbon and R6 and R7 are hydrogen, providinga diacrylamide compound of the formula:

wherein R1, R2, R3, R4, R5, or R6 are independently selected fromhydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl,ether derivatives thereof, or a combination thereof. While the vinylgroups are illustrated as including one or more hydrogens on the vinylgroup can be placed with a halogen, such as chlorine, fluorine, orcombination thereof. In a further example, R1, R2, R3, R4, R5, or R6 canbe a C1-C6 alkyl, such as a methyl, ethyl, propyl or butyl, or etherderivatives thereof. For example, R1, R2, or R3 can be an ethyl, propylor butyl, or ether derivatives thereof or R3, R4, or R5 can be an ethyl,propyl or butyl, or ether derivatives thereof. In particular, the alkylcan be linear or branched. In example, at least one of R1, R2, or R3 canbe a branched alkyl or at least one of R3, R4, or R5 can be a branchedalkyl. For example, propyl includes n-propyl or iso-propyl, and butylincludes n-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additionalexample, R1, R2, R3, R4, R5, or R6 independently can be an aryl, such asa phenyl, tolyl, xylyl, or poly-aryl, such as naphthyl, or etherderivatives thereof. Alternatively, the compound can be an analog of theabove compound, such as a methacrylamide or ethacrylamide analog of theabove compound. In a further example, the compound can be monosilylatedwhere one of the silyl groups of the above formula is replaced with ahydroxide or alkoxy group.

In a particular example of formula VIII, R1, R2, R3, R4, R5, and R6 areethyl, providing a diacrylamide compound having the following formula,which has a log(p) value of 4.92.

In a further example of formula VIII, R1, R3, R4, and R6 are methyl andR2 and R5 are tert-butyl, providing a diacrylamide compound of thefollowing formula, which has a log(p) value of 4.85.

In an additional example of formula VIII, R1, R3, R4, and R6 are methyland R2 and R5 are phenyl, providing a diacrylamide compound of thefollowing formula, which has a log(p) value of 4.79

In another example of a multifunctional acrylamide compound, adiacrylamide has the formula:

wherein R4, R5, or R6 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof, and R1, R2, R3, R7, R8, or R9 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a combinationthereof. While the vinyl groups are illustrated as including hydrogen,one or more hydrogens on the vinyl group can be placed with a halogen,such as chlorine, fluorine, or combination thereof. Alternatively, thecompound can be an analog of the above compound, such as amethacrylamide or ethacrylamide analog of the above compound. In afurther example, the compound can be monosilylated where one of thesilyl groups of the above formula is replaced with a hydroxide or alkoxygroup.

In an example, R5 of formula XII independently can be C1-C6 alkyl, suchas a methyl or ethyl group. In an additional example, R4 or R6 offormula XII independently can be C1-C6 alkyl, such as a methyl or ethylgroup. In another example, R4, R5, or R6 independently can behydroxyalkyl.

In a further example, R1, R2, R3, R7, R8, or R9 independently can beselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl,ether derivatives thereof, or a combination thereof. In a furtherexample, R1, R2, R3, R7, R8, or R9 can be a C1-C6 alkyl, such as amethyl, ethyl, propyl or butyl, or ether derivatives thereof. Forexample, R1, R2, or R3 can be an ethyl, propyl or butyl, or etherderivatives thereof or R7, R8, or R9 can be an ethyl, propyl or butyl,or ether derivatives thereof. In particular, the alkyl can be linear orbranched. In example, at least one of R1, R2, or R3 can be a branchedalkyl or at least one of R7, R8, or R9 can be a branched alkyl. Forexample, propyl includes n-propyl or iso-propyl, and butyl includesn-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additional example,R1, R2, R3, R7, R8, or R9 independently can be an aryl, such as aphenyl, tolyl, xylyl, or poly-aryl, such as naphthyl, or etherderivatives thereof.

In a particular example of formula XII, R5 can be ethyl, providing adiacrylamide compound of the formula:

wherein R4 or R5 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R1, R2, R3, R6, R7, or R8 are independentlyselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl,ether derivatives thereof, or a combination thereof. While the vinylgroups are illustrated as including hydrogen, one or more hydrogens onthe vinyl group can be placed with a halogen, such as chlorine,fluorine, or combination thereof. Alternatively, the compound can be ananalog of the above compound. In a further example, the compound can bemonosilylated where one of the silyl groups of the above formula isreplaced with a hydroxide or alkoxy group.

In an example, R4 or R5 of formula XIII independently can be C1-C6alkyl, such as a methyl or ethyl group. In another example, R4 or R5independently can be hydroxyalkyl.

In a further example, R1, R2, R3, R6, R7, or R8 independently can beselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl,ether derivatives thereof, or a combination thereof. In a furtherexample, R1, R2, R3, R6, R7, or R8 can be a C1-C6 alkyl, such as amethyl, ethyl, propyl or butyl, or ether derivatives thereof. Forexample, R1, R2, or R3 can be an ethyl, propyl or butyl, or etherderivatives thereof or R6, R7, or R8 can be an ethyl, propyl or butyl,or ether derivatives thereof. In particular, the alkyl can be linear orbranched. In example, at least one of R1, R2, or R3 can be a branchedalkyl or at least one of R6, R7, or R8 can be a branched alkyl. Forexample, propyl includes n-propyl or iso-propyl, and butyl includesn-butyl, iso-butyl, sec-butyl, or tert-butyl. In an additional example,R1, R2, R3, R6, R7, or R8 independently can be an aryl, such as aphenyl, tolyl, xylyl, or poly-aryl, such as naphthyl, or etherderivatives thereof.

In a particular example of formula XIII, R4 and R5 are ethyl and R1, R2,R3, R6, R7, and R8 are ethyl, providing a diacrylamide of the followingformula, which has a log(p) value of 4.51.

In another example of formula XIII, R4 and R5 are ethyl, R1, R3, R6, andR8 are methyl, and R2 and R5 are tert-butyl, providing a diacrylamide ofthe following formula, which has a log(p) value of 4.44.

In another example of formula XIII, R4 and R5 are ethyl, R1, R3, R6, andR8 are methyl, and R2 and R5 are phenyl, providing a diacrylamide of thefollowing formula, which has a log(p) value of 4.38.

Alternatively, each of the above compounds I-XVI can be an analog of theillustrated compound. An exemplary analog can include a methacrylamide,an ethacrylamide analog of the above compounds, or combinations thereof.In a further example, those of the above compounds illustrated asincluding two silyl groups can be monosilylated wherein one of the silylgroups is replaced with a hydroxide or alkoxy group.

In an exemplary embodiment, such acrylamide compounds can find use as acrosslinker in a polymerization reaction. In particular, such protecteddiacrylamide crosslinkers can be utilized in polymerization reactionscarried out in non-aqueous hydrophobic solvents. A protecteddiacrylamide can be more hydrophobic than hydrophilic. Whenpolymerization is carried out in an emulsion or similar process, suchprotected diacrylamides can preferentially reside in a hydrophobicphase. For example, an oil-in-water emulsion can be formed in which thepolymerization reaction takes place in the oil dispersed phase. Suchhydrophobic diacrylamide crosslinkers can preferentially reside ortransport to the oil phase to participate in the polymerizationreaction. In another example, a hydrophobic dispersed phase in whichpolymerization occurs can be formed from a promoted polymeric particle,such as a polystyrene or polyacrylate particle promoted with dioctanoylperoxide, dioctyladipate, n-butyl phthalate, dodecanol, polystyrene withmolecular weight below 20 kD, or a combination thereof. Such protecteddiacrylamides can preferentially reside in the hydrophobic dispersedphase.

Such diacrylamide crosslinkers are typically useful in free radicalinitiated polymerization reactions. Exemplary free radical polymerizablemonomers include acrylamide, vinyl acetate, hydroxyalkylmethacrylate, orany combination thereof. Such diacrylamide crosslinkers find useparticularly in such free radical polymerization reactions carried out ahydrophobic phase or solvent.

In an example, a composition includes a diacrylamide crosslinker and afree radical polymerizable monomer in a non-aqueous solution. Thecomposition can include the diacrylamide crosslinker in an amountrelative to the free radical polymerizable monomer in a range of 0.01 wt% to 30 wt %, such as a range of 0.05 wt % to 15 wt %, a range of 0.05wt % to 8 wt %, or even a range of 0.1 wt % to 5 wt %. In a furtherexample, the composition can include an aqueous phase within which thenon-aqueous solution is dispersed, such as in an emulsion.

After polymerization, the resulting polymer can include the silylfunctional groups. The polymer can be deprotected, removing the silylfunctional groups. For example, the polymer can be deprotected throughacid cleaving, leaving hydroxyl groups in place of the silyl groups.

In an example, the above classes of compounds permit deprotection (e.g.,removal of the silyl groups) with limited hydrolysis of the non-silylelements of the compounds. Such a technical advantage is particularlydesirable when polymerizing in a multiphase system (e.g., oil-in-water),when a hydrophilic end product is desired, when exposed hydroxyl groupsare desired in the end product, or any combination thereof.

In a particular example, the estimated logarithm of the partitioncoefficient (n-Octanol/Water) as determined using ChemBioDraw Ultraversion 13.0 using C in place of Si, herein “log(p),” of the compound isgreater than 1.0 and the log(p) of a deprotected analogous compound inwhich the silyl groups are replaced with a hydroxyl group is not greaterthan 1.0. For example, the log(p) of the compound can be at least 1.2,such as at least 1.3, at least 1.5, at least 1.8, or even at least 2.0.The log(p) of the compound can be not greater than 10.0, such as notgreater than 5.0. The log(p) of the analogous compound can be notgreater than 0.8, such as not greater than 0.7, not greater than 0.6,not greater than 0.5, not greater than 0, or even not greater than −0.5.The log(p) of the analogous compound can be at least −10.0, such as atleast −5.0.

Protected multi-acrylamide or diacrylamide compounds, or analogs, can beformed by forming an acrylamide compound or analog having unprotectedhydrophilic groups, followed by protecting the hydrophilic groups.Alternatively, the protected multi-acrylamide or diacrylamide compoundcan be formed by protecting non-amine hydrophilic groups of a compoundincluding multiple amine groups, followed by forming an acrylamide oranalog from the amine groups.

In an example, a silylation reagent, such as silyl chloride, silyltriflate, or silazane, and a hydroxylated diamine compound are mixed ina solvent to form a silyl protected diamine compound. For example, thesilyl chloride can be tert-butyldimethylsilyl chloride, trimethylsilylchloride, triethylsilyl chloride, diphenyl methyl silyl chloride,chlorotriphenylsilane, or a combination thereof. In an example, thesilyl trifluoromethanesulfonates (“triflate”) includetert-butyldimethylsilyl trifluoromethanesulfonate, trimethylsilyltrifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate, or acombination thereof. An example of a silazane includesdiphenylmethyl(dimethylamino)silane. An exemplary hydroxylated diamineincludes alkyl-diyl bis hydroxyalkyl acrylamide, hydroxyalkyldiyl-diacrylamide, bishydroxyalkyl-diyl diacrylamide, a derivativethereof, or a combination thereof. The solvent can include a DMFsolvent. In addition, the mixture can include imidazole or a derivativethereof. The reactive mixture can be stirred for at least 8 hours underan inert atmosphere. The silyl protected diamine compound is extractedand dried. For example, the silyl protected diamine compound can beextracted with diethyl ether or dichloromethane and washed with abuffered aqueous solution.

The silyl protected diamine compound can be mixed with a solutionincluding an activated acrylate, such as acryloyl chloride or acryloylanhydride, or an activated alkylacrylate analog, to form a protecteddiacrylamide compound or analog thereof. The solution can include anorganic solvent, such as an aromatic solvent, a halogenated hydrocarbonsolvent, an alcohol solvent, or a combination thereof. The solution canfurther include a buffering agent, such as a carbonate salt. Forexample, the silyl protected diamine compound in a toluene solvent canbe added slowly to a cooled solution including toluene and acryloylchloride. When mixing, the solution can be maintained at a temperaturein a range of −2° C. to 20° C., such as in a range of −2° C. to 5° C.The protected diacrylamide compound or analog can be extracted using anaqueous solution, precipitated using methanol, and filtered. In anexample, the reaction mixture, extract, precipitate and filtrate aremaintained at a temperature below 40° C., such as below 35° C.,throughout the process. The filtrate can be further purified usingchromatography.

In an alternative example, the silyl protected diamine compound inaqueous-organic two-phase systems can be mixed with an activatedacrylate, such as acryloyl chloride or acryloyl anhydride, to form aprotected diacrylamide compound or analog thereof. The organic phase caninclude an organic solvent such as an aromatic solvent, a halogenatedhydrocarbon solvent, an alcohol solvent or a combination thereof. Theaqueous phase can include a buffering agent, such as a carbonate salt.For example, acryloyl chloride can be added slowly to a cooled two-phasesystem comprised of a dichloromethane solution of the protected diaminecompound and an aqueous solution of K₂CO₃. When mixing, the two-phasesystem can be maintained at a temperature in a range of −2° C. to 20°C., such as in a range of −2° C. to 5° C. The organic phase containingthe protected diacrylamide compound or dialkylacrylamide analog can beseparated from an aqueous phase, washed with water, brine and purifiedusing chromatography.

In an alternative example, a hydroxylated diamine compound including oneor more hydroxyl groups can be mixed with an activated acrylate, such asacryloyl chloride or acryloyl anhydride, or alkylacrylate analog to forma diacrylamide compound or analog. An exemplary hydroxylated diamineincludes alkyl-diyl bis hydroxyalkyl acrylamide, hydroxyalkyldiyl-diacrylamide, bishydroxyalkyl-diyl diacrylamide, a derivativethereof, an analog thereof, or a combination thereof. The solution caninclude an organic solvent, such as an aromatic solvent, a halogenatedhydrocarbon solvent, an alcohol solvent, or a combination thereof. Thesolution can further include a buffering agent, such as a carbonatesalt. For example, a solution including the diamine compound, toluene,and optionally methanol can be added to acryloyl chloride or acryloylanhydride dissolved in toluene. When mixing, the solution can bemaintained at a temperature in a range of −2° C. to 20° C., such as in arange of −2° C. to 5° C. The diacrylamide compound can be extractedusing a buffered aqueous solution, precipitated, and filtered. Thediacrylamide compound can be further purified using dry flashchromatography.

The diacrylamide compound can be re-dissolved and reacted with asilylation reagent, such as silyl chloride, silyl triflate, or silazane,in a solvent to form a protected diacrylamide. For example, the silylchloride can be tert-butyldimethylsilyl chloride, trimethylsilylchloride, triethylsilyl chloride, diphenyl methyl silyl chloride,chlorotriphenylsilane or a combination thereof. In an example, the silyltrifluoromethanesulfonates (“triflate”) include tert-butyldimethylsilyltrifluoromethanesulfonate, trimethylsilyl trifluoromethanesulfonate,triethylsilyl trifluoromethanesulfonate, or a combination thereof. Anexample of a silazane is diphenylmethyl(dimethylamino)silane. Thesolvent can include a DMF solvent. In addition, the mixture can includeimidazole or a derivative thereof. The reactive mixture can be stirredfor at least 8 hours under an inert atmosphere. The product can beextracted and washed.

While the above examples use acryloyl chloride or acryloyl anhydride,amide forming chemistries including N-hydroxysuccinimide (NHS),dicyclohexylcarbodiimide (DCC), N,N′-diisopropylcarbodiimide (DIC), orcombinations thereof can be used in place of reacting with acryloylchloride or anhydride.

EXAMPLES Example 1

t-Butyldimethylsilylchloride (25.23 g, 167 mmol) is added to a mixtureof ethylene diaminoethanol (12.01 g, 81.0 mmol) and imidazole (11.34 g,166 mmol) in DMF (112 mL), in four portions over a period of 50 minutesof which the mixture was cooled in an ice bath the last 25 minutes. Thereaction mixture is diluted with DMF (50 mL) and stirred over night atroom temperature. It is then quenched with water (155 mL), extractedwith diethyl ether (approx. 200 mL), and washed with water (approx. 200mL) and brine (approx. 200 mL), which leads to a crystallineprecipitate. The organic phase is then dried over MgSO4 and evaporated,giving 18.09 g product, yellow oil. The pH in the aqueous phasecontaining precipitate is increased to pH 8-8.5 with 5% NaHCO3. Thisaqueous phase is then extracted with diethyl ether and dried over MgSO4.Evaporation gives a further 3.80 g product.

K₂CO₃ (6.32 g, 45.9 mmol) is added to a solution of acryloyl chloride(3.11 g, 35.2 mmol) in toluene (30 mL). The mixture is cooled in an icebath. A solution of N,N′-bis(2-(t-butyldimethylsilyloxy)ethyl)ethane-1,2-diamine (3.80 g, 10.1 mmol) in toluene(80 mL) is added drop wise over a period of 15 minutes. The reactionmixture is allowed to gradually reach room temperature and is stirredover night for approximately 20 h under an inert atmosphere.

The reaction mixture is cooled in an ice bath, and cold water (150 mL)is added. The product is extracted with diethyl ether and washed with 5%NaHCO₃ and water. The ether phase is dried (MgSO₄). Before evaporation,MEHQ (1.2 mg) is added to the ether phase, and the temperature of thewater bath is kept below 30° C. The crude product is purified by SiO₂column with hexane:EtOAc (8:2 to 1:1). Before evaporation of thefractions, MEHQ (1.5 mg) is added. The temperature of the water bath iskept below 30° C., providing 2.80 g.

Example 2

Acryloyl chloride (38 mL, 0.47 mol) is dissolved in 500 mL toluene at 0°C. before potassium carbonate (89.83 g, 0.65 mol) is added.1,3-Diamino-2-propanol (11.72 g, 0.13 mol) is dissolved in 250 mLtoluene and 50 mL methanol is added drop wise over 30 minutes at 0° C.The reaction mixture is stirred for 2 hours at 0° C. before it is pouredinto 500 mL water while stirring. An amount of 500 mL 0.1M HCl is addedfollowed by 500 mL 0.1M NaOH. The layers are separated and the aqueousphase is reduced to ˜0.4 L using a rotary evaporator, keeping thetemperature in the water bath under 35° C. An amount of 500 mL methanolis added, leading to precipitation. The precipitate is removed byfiltration and the filter cake is washed with 500 mL methanol. Thecombined filtrate is reduced using a rotary evaporator, keeping thetemperature in the water bath under 35° C. The crude product isre-dissolved in 50 mL methanol, 25 g SiO₂ is added, and the mixture isreduced using a rotary evaporator, keeping the temperature in the waterbath under 35° C.

The product mixture is purified using dry flash chromatography on SiO₂with a column diameter of 6.5 cm and column height of 9 cm. The eluentis dichloromethane using a gradient of methanol from 0 to 12.5% toprovide a yield of 12.90 g, 65.1 mmol, 50%.

Example 3

An N,N′-(2-hydroxypropane-1,3-diyl)diacrylamide is formed prior toadding protection groups.

To a solution of acryloyl chloride (34 ml, 0.42 mol) in dry acetonitrile(250 ml) is added potassium carbonate (83.4 g, 0.60 mol), followed byslow addition of a solution 1 of 1,3-diamino-2-propanol (10.6 g, 0.12mol) in dry acetonitrile (450 ml) with stirring at 0° C. After one hour,MeOH (140 ml) is added and the reaction mixture concentrated to a smallvolume. The white suspension is transferred to a column loaded withsilica gel and the product is isolated by dry flash chromatography(DCM:MeOH 95:5-80:20 gradient) to afford 10.75 gram (45%) of the titlecompound as a colorless solid. Sonication and gentle heating are usedfor dissolution.

Example 4

A solution of K₂CO₃ (61.6 g, 446 mmol) in 170 mL of water is added intoa solution ofN¹,N²-bis2-(t-butyldimethylsilyloxy)ethyl)ethane-1,2-diamine (37.3 g,99.1 mmol) in 220 mL of dichloromethane while stirring vigorously at anice bath temperature. Acryloyl chloride (24.2 mL, 298 mmol) is addedinto the above biphasic mixture dropwise over a period of 10 min whilestirring vigorously at an ice-water bath temperature. After addition iscomplete, the solution is stirred an additional 15 min.

The above reaction mixture is transferred to a separating funnel whichcontains 100 mL of dichloromethane. The separated organic layer iswashed with water (2×300 mL) and brine (300 mL). The collected organiclayer is filtered through a Biotage phase separator (150 mL) and isconcentrated under vacuum using bath temperature below 20° C. Theresulting crude product is purified by Biotage SNAP 340 column elutionwith first 10% ethyl acetate in hexane followed by 10-50% ethyl acetatein hexane. To the combined desired fractions is added about 9 mg of MEHQbefore evaporation. The temperature of the water bath is kept below 30°C., providing a pure desired product, 30.5 g (63% yield).

Example 5

A silyl protected acrylamide monomer,(N-(2-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide) (tBDMS-HEAM), ispolymerized with aN,N′-(ethane-1,2-diyl)bis(N-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide(tBDMS EBHEAM) crosslinker in a dispersed phase formed from polystyreneparticles and is deprotected to form a hydrogel particle.

A concentrated PVA solution is formed from 80 g polyvinylalcohol (PVA)slowly added to 2000 g water, followed by stirring and heating to 80° C.for 1 hour and cooling.

To 88 g of the concentrated PVA solution, 785 g water, 0.88 g SDS, and3.33 g borax are added to from a PVA borax solution.

A monomer emulsion is formed from 7.82 g toluene, 0.040 g2,2′-azobis-(2-methylbutyronitrile) (AMBN), 2.06 g tBDMS HEAM, 0.51 gtBDMS-EBHEAM (95 purity) and 92.9 g PVA borax solution mixed byultraturax for 2 minutes, and further homogenized for 5 minutes.

In a 0.5 L reactor, 1.65 g of a water dispersion of seed particles (seeddiameter 0.319 μm, 8.07 weight % solids) is mixed with 88.34 g of themonomer emulsion. Argon gas (10-20 ml/min) is bubbled through themixture while stirring and heating 1 hour at 30° C. and 2 hours at 40°C. The argon flow is stopped, and heating and stirring continued for 3hours at 80° C.

The reaction mixture is transferred to a 1 liter centrifugation flaskand centrifuged in a Sorvall RC3CPlus centrifuge for 50 minutes at 4500RPM. The creamy flotation product is collected and is centrifuged twicein THF.

To 83.9 g of the THF swollen gel sediment, the same weight of glacialacetic acid and half the weight of water is added. The mixture is shakenat room temperature overnight. The gel is worked by removing thesupernatant after centrifugation and adding THF and water in a ratio ofTHF:water 1:1 two times and water once, followed by three times withDMF.

The solids content of the dispersion is determined to be 1.63 g. Thediameter of a water swollen gel can be measured in a microscope withphase contrast equipment and is on average 1.6 μm. The CV is not greaterthan 5.0%.

Example 6

A silyl protected acrylamide monomer,(N-(2-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide) (tBDMS-HEAM), ispolymerized with a tBDMS-EBHEAM crosslinker in a dispersed phase formedfrom polystyrene particles and is deprotected to form a hydrogelparticle.

A concentrated PVA solution is formed from 80 g polyvinylalcohol (PVA)slowly added to 2000 g water, followed by stirring and heating to 80° C.for 1 hour and cooling.

To 88 g of the concentrated PVA solution, 785 g water, 0.88 g SDS, and3.33 g borax is added to form a PVA borax solution.

A monomer emulsion is formed from 7.82 g toluene, 0.040 g2,2′-azobis-(2-methylbutyronitrile) (AMBN), 2.06 g tBDMS HEAM, 0.96 gtBDMS-EBHEAM (95 purity) and 92.9 g PVA borax solution mixed byultraturax for 2 minutes, and further homogenized for 5 minutes.

In a 0.5 L reactor, 1.65 g of a water dispersion of seed particles (seeddiameter 0.319 μm, 8.07 weight % solids) is mixed with 88.34 g of themonomer emulsion. Argon gas (10-20 ml/min) is bubbled through themixture while stirring and heating 1 hour at 30° C. and 2 hours at 40°C. The argon flow is stopped, and heating and stirring continued for 3hours at 80° C.

The reaction mixture is transferred to a 1 liter centrifugation flaskand centrifuged in a Sorvall RC3CPlus centrifuge for 50 minutes at 4500RPM. The creamy flotation product is collected and is centrifuged twicein THF.

To 83.9 g of the THF swollen gel sediment, the same weight of glacialacetic acid and half the weight of water is added. The mixture is shakenat room temperature over night. The gel is worked by removing thesupernatant after centrifugation and adding THF and water in a ratio ofTHF:water 1:1 two times and water once, followed by three times withDMF.

The solids content of the dispersion is determined to be 1.63 g. Thediameter of a water swollen gel can be measured in a microscope withphase contrast equipment and is on average 1.6 μm. The CV is not greaterthan 5.0%.

Example 7

A silyl protected acrylamide monomer,(N-(2-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide) (tBDMS-HEAM), ispolymerized withN,N′-(ethane-1,2-diyl)bis(N-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide)(TBDMS EBHEAM) as crosslinker in a dispersed phase formed frompolystyrene particles and is deprotected to form a hydrophilic particle.

A concentrated PVA solution is prepared by adding 80 g polyvinylalcohol(PVA) slowly to 2000 g water while stirring. The mixture is stirred andis heated to 80° C. for 1 hour and cooled.

To 241.8 g of the concentrated PVA solution, 2129.6 g water, 2.32 g SDSand 9.97 g borax are added to form a PVA borax solution.

A monomer emulsion is prepared by mixing 72.68 g toluene, 0.29 g2,2′-azobis-(2-methylbutyronitrile) (AMBN), 14.59 g tBDMS HEAM, 4.46 gTBDMS EBHEAM and 835.8 g PVA borax solution, mixed by ultraturax for 2minutes, and further homogenized for 9 minutes in a high pressureGauline APV-100 homogenizer at 400 Bar.

In a 1 L reactor, 16.86 g of a water dispersion of seed particles (seeddiameter 0.319 μm, 8.07 weight % solids) is mixed with 897 g of themonomer emulsion. The mixture is stirred and heated for 3 hour at 40° C.while bubbling argon through the mixture at 0.05 l/min for the first 2hours and at 0.15 L/min for 1 hour. The argon flow is then stopped andthe emulsion is heated for 3 hours at 80° C.

The reaction mixture is transferred to a 1 liter centrifugation flaskand centrifuged in a Sorvall RC3CPlus centrifuge for 60 minutes at 4700RPM. The creamy flotation product is transferred to a new 500 mL glassflask and resuspended to 370.74 g with water, the pH is adjusted to 3.86with 21.09 g 0.5 M acetic acid. The mixture is stirred at 60° C. for 2hours.

The gel is worked up by adding 9 volumes of THF to the deprotected gel,and centrifuged in a Sorvall RC3CPlus centrifuge for 10 minutes at 3500RPM, followed by two centrifugations with DMF and two centrifugationswith dry DMF, all with addition of 7.5% THF prior to centrifugation. Thesolids content of the gel in DMF is determined to be 6.37 g. The beaddispersion is transferred to water and inspected by microscopy and thebead diameter is 1.7 micron in water.

Example 8

A silyl protected acrylamide monomer,(N-(2-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide) (tBDMS-HEAM), ispolymerized with a tBDMS-EBHEAM crosslinker in a dispersed phase formedfrom polystyrene particles and is deprotected to form a hydrogelparticle.

An emulsion is prepared by first dissolving 1.74 g SDS in 290.00 g waterand then adding 14.50 g acetone and 29.00 g bis(2-ethylhexyl) adipate(DOA). The emulsion is mixed by ultraturax for 2 minutes, and furtherhomogenized for 5.6 minutes in a high pressure Gauline APV-100homogenizer at 400 Bar.

31.14 g of this emulsion is added to 43.89 g of seed particles (seeddiameter 0.140 μm, 4.85 weight % solids) in a flask. The mixture isshaken at 40° C. for 40 h in a shaking bath for activation.

An SDS borax solution is prepared by dissolving 4.54 g SDS and 9.69 gborax to 2369.8 g water.

A monomer emulsion is formed from 125.29 g 2-phenethyl acetate, 0.468 g2,2′-azobis-(2-methylbutyronitrile) (AMBN), 19.51 g tBDMS HEAM, 5.99 gtBDMS-EBHEAM and 816.75 g SDS borax solution mixed by ultraturax for 5minutes, and further homogenized for 9.68 minutes.

In a 1 L reactor, 62.53 g of a water dispersion of activated seedparticles is mixed with 938.1 g of the monomer emulsion. The mixture isstirred and heated at 40° C. for 2 h. The mixture is further stirred andheated at 40° C. for another hour while argon gas (150-200 ml/min) isbubbled through the mixture. The amount of O₂ in the emulsion at thispoint is measure to be 0 ppb. The argon flow is stopped, and heating andstirring continued for 10 hours at 70° C.

The reaction mixture is transferred to four 250 mL centrifugation flasksand centrifuged in a Beckman Coulter Avanti J-20 XP centrifuge for 60minutes at 13000 RPM. The supernatants are discarded and the sedimentsare collected and transferred into a glass flask by adding water.

pH of the aqueous dispersion of gels is adjusted to 3.8 by adding 0.5 Macetic acid solution. The acidified gel dispersion is shaken at 60° C.in a shaking bath for 2 h and cooled.

The gel dispersion is transferred into three 1 L flasks, 300 g THF isadded to each, the flasks are shaken at room temperature for 30 min on ashaking table and centrifuged in a Thermo Scientific Thermo ScientificSorvall RC3CPlus centrifuge for 25 minutes at 4500 RPM. The upper phasesof resulting biphasic mixtures are discarded, 50 g THF is added to eachflask, the flasks are shaken at room temperature for 30 min on a shakingtable and centrifuged for 25 minutes at 4500 RPM. Supernatants arediscarded.

Contents of each flask are divided into two 250 mL centrifuge flasks.Approximately 100 g DMF is added on each flask and the flasks are shakenovernight at room temperature on a shaking table. Contents of each flaskare totaled to 200 g by adding 20 g THF and necessary amount of DMF. Theflasks are centrifuged in a Beckman Coulter Avanti J-20 XP centrifugefor 70 minutes at 13000 RPM. Supernatants are discarded.

Approximately 100 g DMF is added on each flask and the flasks are shakenfor 40 min at room temperature on a shaking table. Contents of eachflask are totaled to 200 g by adding 20 g THF and necessary amount ofDMF. The flasks are centrifuged in a Beckman Coulter Avanti J-20 XPcentrifuge for 70 minutes at 13000 RPM. Supernatants are discarded andall the sediments are combined into a new flask by using minimal amountsof DMF.

The solids content of the dispersion is determined to be 2.34 g. Thediameter of a water swollen gel is measured in a microscope with phasecontrast equipment and is on average 0.80 μm.

Water swollen gel is further analyzed in a disc centrifuge instrument(CPS Instruments, Inc, model DC20000) using a gradient of 3 and 7 w %sucrose solutions and a rotation speed of 15000 RPM. The diameter ismeasured as 0.4995 μm using a particle density of 1,032 g/ml. CV(number) is measured as 3.6%.

Example 9

A silyl protected acrylamide monomer,(N-(2-((tert-butyldimethylsilyl)oxy)ethyl)acrylamide) (tBDMS-HEAM), ispolymerized with a tBDMS-EBHEAM crosslinker in a dispersed phase formedfrom polystyrene particles and is deprotected to form a hydrogelparticle.

An emulsion is prepared by first dissolving 1.98 g SDS in 330.05 g waterand then adding 16.51 g acetone and 33.00 g DOA. The emulsion is mixedby ultraturax for 2 minutes, and further homogenized for 6.4 minutes ina high pressure Gauline APV-100 homogenizer at 400 Bar.

37.71 g of this emulsion is added to 68.57 g of seed particles (seeddiameter 0.081 μm, 4.91 weight % solids) in a flask. The mixture isshaken at 40° C. for 20 h in a shaking bath for activation.

An SDS borax solution is prepared by dissolving 3.77 g SDS and 7.59 gborax to 1975.6 g water.

A monomer emulsion is formed from 33.89 g 2-phenethyl acetate, 0.126 g2,2′-azobis-(2-methylbutyronitrile) (AMBN), 5.26 g tBDMS HEAM, 1.61 gtBDMS-EBHEAM and 223.32 g SDS borax solution mixed by ultraturax for 5minutes, and further homogenized for 2.6 minutes.

In a 250 mL reactor, 20.31 g of a water dispersion of activated seedparticles is mixed with 228.23 g of the monomer emulsion. The mixture isstirred and heated at 40° C. for 2 h. The mixture is further stirred andheated at 40° C. for another hour while argon gas (150-200 ml/min) isbubbled through the mixture. The amount of O₂ in the emulsion at thispoint is measure to be 230 ppb. The argon flow is stopped, and heatingand stirring continued for 10 hours at 70° C.

The reaction mixture is transferred to a 250 mL centrifugation flask andcentrifuged in a Beckman Coulter Avanti J-20 XP centrifuge for 90minutes at 12500 RPM. The supernatant is discarded and the sediment iscollected and transferred into a glass flask by adding water.

pH of the aqueous dispersion of gels is adjusted to 3.85 by adding 0.5 Macetic acid solution. The acidified gel dispersion is shaken at 60° C.in a shaking bath for 2.5 h and cooled.

The gel dispersion is transferred into a 1 L flask, 170.06 g THF isadded, the flask is shaken at room temperature for 10 min on a shakingtable and centrifuged in a Thermo Scientific Thermo Scientific SorvallRC3CPlus centrifuge for 30 minutes at 4500 RPM. The upper phase ofresulting biphasic mixture is discarded. 86.81 g THF is added, the flaskis shaken at room temperature for 15 min on a shaking table andcentrifuged for 30 minutes at 4500 RPM. Supernatant is discarded.

200 g DMF is added on the gel sediment in 1 L flask and this suspensionis divided in two 250 mL centrifuge flasks. The flasks are shaken atroom temperature for 153 min on a shaking table and contents of eachflask are totaled to 200 g by adding 30 g THF and necessary amount ofDMF. The flasks are centrifuged in a Beckman Coulter Avanti J-20 XPcentrifuge for 90 minutes at 14000 RPM. Supernatants are discarded.

100 g DMF is added to each flask and the suspensions are shaken at roomtemperature for 20 min on a shaking table. Contents of each flask aretotaled to 200 g by adding 30 g THF and necessary amount of DMF and theflasks are centrifuged in a Beckman Coulter Avanti J-20 XP centrifugefor 90 minutes at 14000 RPM. Supernatants are discarded and all thesediments are combined into a new flask by using minimal amounts of DMF.The solids content of the dispersion is determined to be 2.03 g.

Water swollen gel is further analyzed in a disc centrifuge instrument(CPS Instruments, Inc, model DC20000) using a gradient of 3 and 7 w %sucrose solutions and a rotation speed of 20000 RPM. The diameter ismeasured as 0.2885 μm using a particle density of 1.032 g/ml. CV(number) is measured as 5.56%.

Particular embodiments of the above-described protective diacrylamidecompound exhibit particular technical advantages over othercrosslinkers. For example, such protected diacrylamide compounds can beutilized during polymerization reactions in hydrophobic solvents. In thecontext of an emulsion, such protected diacrylamide compoundspreferentially reside within hydrophobic phase, whether the dispersedphase or the continuous phase. Diacrylamide compounds protected withsilyl protection groups including at least one ethyl, propyl, or butylfunctionality provide advantageous preference for hydrophobic phases. Inanother example, diacrylamide compounds protected with silyl protectiongroups including at least one branched alkyl functionality provideadvantageous preference for hydrophobic phases. In particular,diacrylamide compounds having a log(p) value within a desirable rangeadvantageously reside in a hydrophobic phase and are particularly usefulin emulsion polymerization. When the resulting polymer is desirablyhydrophilic, it is preferred that the diacrylamide analogous compoundhave a log(p) value within a desirable range.

In a first aspect, a compound has formula I above or an analog thereof,wherein R1 and R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R3, R4, R5, R6, and R7 are independentlyselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl,oxycarbonyl, aryl, ether derivatives thereof, a silyl, or a combinationthereof.

In an example of the first aspect, R1 or R2 is a C1-C6 alkyl. Forexample, R1 or R2 is a methyl or ethyl group.

In another example of the first aspect and the above examples, at leastone of R3, R4, R5, R6, and R7 is an aryl group. For example, the arylgroup can be phenyl, tolyl, xylyl, or poly-aryl, or an ether derivativethereof. In particular, the aryl group can be tolyl.

In a further example of the first aspect and the above examples, atleast one of R3, R4, R5, R6, and R7 is alkyl, or an ether derivativethereof. The alkyl can be a C1-C6 alkyl or an ether derivative thereof.For example, the alkyl group can be a methyl, ethyl, propyl, butyl,ether derivative thereof, or combination thereof, such as ethyl, propyl,butyl, ether derivative thereof, or combination thereof. In particular,the alkyl can be butyl and the butyl is tert-butyl.

In an additional example of the first aspect and the above examples, R6or R7 is hydrogen.

In another example of the first aspect and the above examples, thelog(p) of the compound is greater than 1.0, at least 1.2, at least 1.3,at least 1.50, at least 1.7, or at least 2.0. The log(p) of the compoundmay be not greater than 10.0, such as not greater than 5.0. Further, thelog(p) of a deprotected analogous compound is not greater than 0.5 notgreater than 0.3, not greater than 0.2, not greater than 0.1, notgreater than 0, not greater than −0.5, or not greater than −1.0. Thelog(p) of a deprotected analogous compound is at least −10.0, such as atleast −5.0.

In a second aspect, a compound has the formula II above or an analogthereof, wherein R1 or R2 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof, and R3, R4, or R5 are independentlyselected from alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl,ether derivatives thereof, or a combination thereof.

In an example of the second aspect, R1 or R2 is a C1-C6 alkyl, or anether derivative thereof. For example, R1 or R2 is a methyl or ethylgroup.

In another example of the second aspect and the above example, at leastone of R3, R4, R5, is aryl or an ether derivative thereof. The arylgroup can be phenyl, tolyl, xylyl, or poly-aryl, or an ether derivativethereof. For example, the aryl group can be tolyl.

In a further example of the second aspect and the above examples, atleast one of R3, R4, or R5 is alkyl or an ether derivative thereof. Forexample, the alkyl is a C1-C6 alkyl or an ether derivative thereof. Inparticular, the alkyl group can be a methyl, ethyl, propyl, butyl, etherderivative thereof, or a combination thereof, such as an ethyl, propyl,butyl, ether derivative thereof, or a combination thereof. For example,the alkyl is butyl and the butyl is tert-butyl.

In an additional example of the second aspect and the above examples,the log(p) of the compound is greater than 1.0, at least 1.2, at least1.3, at least 1.5, at least 1.7, or at least 2.0. The log(p) of thecompound can be not greater than 10.0, such as not greater than 5.0.Further, the log(p) of a deprotected analogous compound is not greaterthan 0.5, not greater than 0.3, not greater than 0.2, not greater than0.1, not greater than 0, not greater than −0.5, or not greater than−1.0. The log(p) of the deprotected analogous compound can be at least−10.0, such as at least −5.0.

In a third aspect, a compound has the formula III above or an analogthereof, R1, R2, or R3 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof.

In an example of the third aspect, at least one of R1, R2 or R3 is arylor an ether derivative thereof. For example, the aryl group can bephenyl, tolyl, xylyl, or poly-aryl, or an ether derivative thereof.

In another example of the third aspect or the above example, at leastone of R1, R2 or R3 is an alkyl group or an ether derivative thereof.For example, the alkyl group can be a methyl, ethyl, propyl, or butyl,an ether derivative thereof, or a combination thereof, such as an ethyl,propyl, butyl, ether derivative thereof, or a combination thereof. In anexample, the alkyl group is methyl or ethyl. In an additional example,the alkyl group is tert-butyl.

In a further example of the third aspect or the above examples, thelog(p) of the compound is greater than 1.0, at least 1.2, at least 1.3,at least 1.5, at least 1.7, or at least 2.0. The log(p) of the compoundis not greater than 10.0, such as not greater than 5.0. Further, thelog(p) of a deprotected analogous compound is not greater than 0.5, notgreater than 0.3, not greater than 0.2, not greater than 0.1, notgreater than 0, not greater than −0.5, or not greater than −1.0. Thelog(p) of the deprotected analogous compound is at least −10.0, such asat least −5.0.

In a fourth aspect, a compound has the formula XII above or an analogthereof or monosilylated derivative thereof, wherein R4, R5, or R6 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a combinationthereof, and R1, R2, R3, R7, R8, or R9 are independently selected fromalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, etherderivatives thereof, or a combination thereof.

In an example of the fourth aspect, R4, R5 or R6 is a C1-C6 alkyl or anether derivative thereof. For example, R4, R5 or R6 is methyl or ethyl.

In another example of the fourth aspect or the above example, at leastone of R1, R2, R3, R7, R8, or R9 is aryl or an ether derivative thereof.For example, the aryl group is phenyl, tolyl, xylyl, or poly-aryl, or anether derivative thereof.

In an additional example of the fourth aspect or the above examples, atleast one of R1, R2, R3, R7, R8, or R9 is alkyl or an ether derivativethereof. For example, the alkyl can be a methyl, ethyl, propyl, orbutyl, or an ether derivative thereof. The alkyl can be methyl or ethyl.In another example, the alkyl is tert-butyl.

In a further example of the fourth aspect or the above examples, thelog(p) of the compound is greater than 2.0, at least 2.2, at least 2.3,at least 2.5, at least 2.7, or at least 3.0. The log(p) of the compoundis not greater than 10.0, such as not greater than 5.0. Further, thelog(p) of a deprotected analogous compound is not greater than 0.5, notgreater than 0.3, not greater than 0.2, not greater than 0.1, notgreater than 0, not greater than −0.5, or not greater than −1.0. Thelog(p) of the deprotected analogous compound is at least −10.0, such asat least −5.0.

In a fifth aspect, a compound has the formula XIII above or an analogthereof or monosilylated derivative thereof, wherein R4 or R5 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a combinationthereof, and R1, R2, R3, R6, R7, or R8 are independently selected fromalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, etherderivatives thereof, or a combination thereof.

In an example of the fifth aspect, R4 or R5 is methyl or ethyl.

In another example of the fifth aspect and the above example, at leastone of R1, R2, R3, R6, R7, or R8 is aryl or an ether derivative thereof.

In an additional example of the fifth aspect or the above examples, thearyl group is phenyl, tolyl, xylyl, or poly-aryl, or an ether derivativethereof. For example, the aryl group can be tolyl.

In a further example of the fifth aspect or the above examples, at leastone of R1, R2, R3, R6, R7, or R8 is alkyl or an ether derivativethereof. For example, the alkyl group can be a methyl, ethyl, propyl, orbutyl or an ether derivative thereof, such as an ethyl, propyl, or butylor an ether derivative thereof. The alkyl group can be methyl or ethyl.In another example, the alkyl group can be tert-butyl group.

In another example of the fifth aspect or the above examples, the log(p)of the compound is greater than 2.0, at least 2.2, at least 2.3, atleast 2.5, at least 2.7, or at least 3.0. The log(p) of the compound isnot greater than 10.0, such as not greater than 5.0. Further, the log(p)of a deprotected analogous compound is not greater than 0.5, not greaterthan 0.3, not greater than 0.2, not greater than 0.1, not greater than0, not greater than −0.5, or not greater than −1.0. The log(p) of thedeprotected analogous compound is at least −10.0, such as at least −5.0.

In a sixth aspect, a compound has the formula VII above or an analogthereof or monosilylated derivative thereof, wherein R1 or R2 areindependently selected from alkyl, heteroalkyl, cycloalkyl,hydroxyalkyl, acyl, aryl, ether derivatives thereof, or a combinationthereof or represent a direct bond between a nitrogen and a hydroxylatedcarbon, and R3, R4, R5, R6, R7, R8, R9, or R10 are independentlyselected from hydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl,acyl, oxycarbonyl, aryl, ether derivatives thereof, silyl, or acombination thereof.

In an example of the sixth aspect, at least one of R1 or R2 is alkyl.For example, at least one of R1 or R2 can be methyl or ethyl.

In another example of the sixth aspect or the above examples, at leastone of R3, R4, R5, R6, R7, R8, R9, or R10 is aryl or an ether derivativethereof. For example, at least one of R3, R4, R5, R6, R7, R8, R9, or R10can be phenyl, tolyl, xylyl, or poly-aryl, or an ether derivativethereof.

In a further example of the sixth aspect or the above examples, at leastone of R3, R4, R5, R6, R7, R8, R9, or R10 can be alkyl or an etherderivative thereof. For example, at least one of R3, R4, R5, R6, R7, R8,R9, or R10 can be methyl, ethyl, propyl, or butyl, an ether derivativethereof, or a combination thereof. In an example, at least one of R3,R4, R5, R6, R7, R8, R9, or R10 is a methyl or ethyl group. In anotherexample, at least one of R3, R4, R5, R6, R7, R8, R9, or R10 istert-butyl.

In an additional example of the sixth aspect or the above examples, R6or R7 is hydrogen. In an alternative example of the sixth aspect or theabove examples, R6 or R7 are a C1-C6 alkyl or ether derivative thereof.

In another example of the sixth aspect or the above examples, the log(p)of the compound is greater than 2.5, at least 2.7, at least 2.8, atleast 3.0, at least 3.2, or at least 3.5. Further, the log(p) of adeprotected analogous compound is not greater than 0.5, not greater than0.3, not greater than 0.2, not greater than 0.1, not greater than 0, notgreater than −0.5, or not greater than −1.0.

In a seventh aspect, a method of forming a compound includes mixing anactivated acrylate and a hydroxylated diamine compound to form ahydroxylated diacrylamide compound, separating the hydroxylateddiacrylamide compound, and mixing a silylation reagent, such as silylchloride, silyl triflate, or silazane, with the hydroxylateddiacrylamide compound under reactive conditions to form a silylprotected diacrylamide compound.

In an example of the seventh aspect, the activated acrylate is acryloylchloride, acryloyl anhydride, an alkylacryloyl analog thereof, or acombination thereof.

In another example of the seventh aspect and the above example, mixingthe activate acrylate and the hydroxylated diamine compound includesmixing in an organic solvent. For example, the organic solvent includesan aromatic solvent, a halogenated hydrocarbon solvent, an alcoholsolvent, or a combination thereof.

In a further example of the seventh aspect and the above examples,mixing the activated acrylate and the hydroxylated diamine compoundincludes mixing at a temperature in a range of −2° C. to 20° C. Forexample, the temperature can be in a range of −2° C. to 5° C.

In an additional example of the seventh aspect and the above examples,separating includes precipitating the hydroxylated diacrylamide compoundand filtering the precipitate.

In another example of the seventh aspect and the above examples, thesilyl chloride is tert-butyldimethylsilyl chloride, trimethylsilylchloride, triethylsilyl chloride, diphenyl methyl silyl chloride,chlorotriphenylsilane or a combination thereof. In an example of theseventh aspect and the above examples, the silyltrifluoromethanesulfonates (“triflate”) includes tert-butyldimethylsilyltrifluoromethanesulfonate, trimethylsilyl trifluoromethanesulfonate,triethylsilyl trifluoromethanesulfonate, or a combination thereof. Anexample of a silazane includes diphenylmethyl(dimethylamino)silane.

In a further example of the seventh aspect and the above examples, thehydroxylated diacrylamide is alkyl-diyl bis hydroxyalkyl acrylamide,hydroxyalkyl diyl-diacrylamide, bishydroxyalkyl-diyl diacrylamide, aderivative thereof, or a combination thereof.

In an eighth aspect, a method of forming a compound includes mixing asilylation reagent, such as silyl chloride, silyl triflate, or silazane,with a hydroxylated diacrylamide under reactive conditions to form silylprotected diacrylamide in a solution and separating the silyl protecteddiacrylamide from the solution.

In an example of the eighth aspect, the silyl chloride istert-butyldimethylsilyl chloride, trimethylsilyl chloride, triethylsilylchloride, diphenyl methyl silyl chloride, chlorotriphenylsilane or acombination thereof. In an example of the eighth aspect and the aboveexamples, the silyl trifluoromethanesulfonates (“triflate”) includestert-butyldimethylsilyl trifluoromethanesulfonate, trimethylsilyltrifluoromethanesulfonate, triethylsilyl trifluoromethanesulfonate, or acombination thereof. An example of a silazane includesdiphenylmethyl(dimethylamino)silane.

In a ninth aspect, a method of forming a compound includes mixing asilylation reagent, such as silyl chloride, silyl triflate, or silazane,with a hydroxylated diamine compound under first reactive conditions toform a product in a first solution, separating the product from thefirst solution, and mixing the product with an activated acrylate undersecond reactive conditions in a second solution to form a silylprotected diacrylamide compound.

In an example of the ninth aspect, the activated acrylate is acryloylchloride, acryloyl anhydride, an alkylacryloyl analog thereof, or acombination thereof.

In another example of the ninth aspect and the above example, the silylchloride is tert-butyldimethylsilyl chloride, trimethylsilyl chloride,triethylsilyl chloride, diphenyl methyl silyl chloride,chlorotriphenylsilane or a combination thereof. In an example of theninth aspect and the above examples, the silyltrifluoromethanesulfonates (“triflate”) includes tert-butyldimethylsilyltrifluoromethanesulfonate, trimethylsilyl trifluoromethanesulfonate,triethylsilyl trifluoromethanesulfonate, or a combination thereof. Anexample of a silazane includes diphenylmethyl(dimethylamino)silane.

In a further example of the ninth aspect and the above examples, thehydroxylated diamine is alkyl-diyl bis hydroxyalkyl acrylamide,hydroxyalkyl diyl-diacrylamide, bishydroxyalkyl-diyl diacrylamide, aderivative thereof, or a combination thereof.

In an additional example of the ninth aspect and the above examples,mixing the product with the activated acrylate includes mixing in anorganic solvent. For example, the organic solvent includes an aromaticsolvent, a halogenated hydrocarbon solvent, an alcohol solvent, or acombination thereof.

In another example of the ninth aspect and the above examples, mixingthe product and the activated acrylate includes mixing at a temperaturein a range of −2° C. to 20° C. For example, the temperature can be in arange of −2° C. to 5° C.

In a further example of the ninth aspect and the above examples, thefirst solution includes a DMF solvent. In another example of the ninthaspect and the above examples, the first solution includes imidazole ora derivative thereof. In an additional example of the ninth aspect andthe above examples, the second solution includes a buffering agent. In afurther example of the ninth aspect and the above examples, separatingincludes extracting with diethyl ether or dichloromethane.

In a tenth aspect, a method of forming a polymer includes mixing in ahydrophobic phase, a monomer and a compound of the above aspects, themonomer and the compound polymerizing to form the polymer.

In an example of the tenth aspect, the monomer is a free radicalpolymerizable monomer. For example, the free radical polymerizablemonomer can be acrylamide, vinyl acetate, hydroxyalkylmethacrylate, orany combination thereof.

In another example of the tenth aspect and the above example, thehydrophobic phase is a dispersed phase in an emulsion.

In a further example of the tenth aspect and the above examples, thepolymer includes the silyl group of the compound and wherein the methodfurther includes removing the silyl group from the polymer.

In an eleventh aspect, a composition includes a non-aqueous solutionincluding a diacrylamide crosslinker and a free radical polymerizablemonomer. In an example of the eleventh aspect, the diacrylamidecrosslinker is included in an amount relative to the free radicalpolymerizable monomer in a range of 0.01 wt % to 30 wt %. In a furtherexample of the eleventh aspect and the above example, the compositionfurther includes an aqueous phase, the non-aqueous solution dispersedwithin the aqueous phase as an emulsion.

Note that not all of the activities described above in the generaldescription or the examples are required, that a portion of a specificactivity may not be required, and that one or more further activitiesmay be performed in addition to those described. Still further, theorder in which activities are listed are not necessarily the order inwhich they are performed.

In the foregoing specification, the concepts have been described withreference to specific embodiments. However, one of ordinary skill in theart appreciates that various modifications and changes can be madewithout departing from the scope of the invention as set forth in theclaims below. Accordingly, the specification and figures are to beregarded in an illustrative rather than a restrictive sense, and allsuch modifications are intended to be included within the scope ofinvention.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a process,method, article, or apparatus that comprises a list of features is notnecessarily limited only to those features but may include otherfeatures not expressly listed or inherent to such process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive-or and not to an exclusive-or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

Also, the use of “a” or “an” are employed to describe elements andcomponents described herein. This is done merely for convenience and togive a general sense of the scope of the invention. This descriptionshould be read to include one or at least one and the singular alsoincludes the plural unless it is obvious that it is meant otherwise.

Benefits, other advantages, and solutions to problems have beendescribed above with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any feature(s) that maycause any benefit, advantage, or solution to occur or become morepronounced are not to be construed as a critical, required, or essentialfeature of any or all the claims.

After reading the specification, skilled artisans will appreciate thatcertain features are, for clarity, described herein in the context ofseparate embodiments, may also be provided in combination in a singleembodiment. Conversely, various features that are, for brevity,described in the context of a single embodiment, may also be providedseparately or in any subcombination. Further, references to valuesstated in ranges include each and every value within that range.

What is claimed is:
 1. A compound of the formula:

wherein R1 and R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R3, R4, R5, R6, and R7 are independentlyselected from hydrogen, alkyl, heteroalkyl, cycloalkyl, hydroxyalkyl,acyl, oxycarbonyl, aryl, ether derivatives thereof, a silyl, or acombination thereof.
 2. The compound of claim 1, wherein R1 or R2 is aC1-C6 alkyl.
 3. The compound of claim 2, wherein R1 or R2 is a methyl orethyl group.
 4. The compound of claim 1, wherein at least one of R3, R4,R5, R6, and R7 is an aryl group.
 5. The compound of claim 4, wherein thearyl group is phenyl, tolyl, xylyl, or poly-aryl, or an ether derivativethereof.
 6. The compound of claim 4, wherein the aryl group is tolyl. 7.The compound of claim 1, wherein at least one of R3, R4, R5, R6, and R7is alkyl, or an ether derivative thereof.
 8. The compound of claim 7,wherein the alkyl is a C1-C6 alkyl or an ether derivative thereof. 9.The compound of claim 7, wherein the alkyl group is a methyl, ethyl,propyl, butyl, ether derivative thereof, or combination thereof.
 10. Thecompound of claim 9, wherein the alkyl is butyl and the butyl istert-butyl.
 11. The compound of claim 1, R6 or R7 is hydrogen.
 12. Thecompound of claim 1, wherein the log(p) of a deprotected analogouscompound is not greater than 0.5 and at least −10.0.
 13. The compound ofclaim 12, wherein the log(p) of the compound is greater than 1.0 and notgreater than 10.0.
 14. A compound of the formula:

wherein R1 or R2 are independently selected from alkyl, heteroalkyl,cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivatives thereof, or acombination thereof, and R3, R4, or R5 are independently selected fromalkyl, heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, etherderivatives thereof, or a combination thereof.
 15. The compound of claim14, wherein at least one of R3, R4, and R5 is an aryl group.
 16. Thecompound of claim 15, wherein the aryl group is phenyl, tolyl, xylyl, orpoly-aryl, or an ether derivative thereof.
 17. The compound of claim 15,wherein the aryl group is tolyl.
 18. The compound of claim 14, whereinat least one of R3, R4, and R5 is alkyl, or an ether derivative thereof.19. The compound of claim 18, wherein the alkyl is a C1-C6 alkyl or anether derivative thereof.
 20. A compound of the formula:

wherein R1, R2, or R3 are independently selected from alkyl,heteroalkyl, cycloalkyl, hydroxyalkyl, acyl, aryl, ether derivativesthereof, or a combination thereof.